Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials

Abstract

AIM: We conducted this systematic review and meta-analysis to investigate the efficacy and safety of gefapixant, a novel P2X3 receptor antagonist, in patients with chronic cough. METHODS: We searched four databases for randomized controlled trials (RCTs). We assessed the cough frequency, severity, total Leicester cough questionnaire (LCQ) score, and adverse events. We analyzed the data using Open Meta-Analyst and Review Manager Software. RESULTS: We included four unique studies (comprising five stand-alone RCTs) with 439 patients. Compared to placebo, gefapixant had positive anti-tussive effects by improving awake cough frequency (mean difference [MD] = -5.27, 95% confidence interval [CI] [-6.12, -4.42], P < 0.00001), night cough frequency (MD = -3.71, 95% CI [-6.57, -0.85], P = 0. 01), 24 h cough frequency (MD = -4.18, 95% CI [-5.01, -3.36], P < 0.00001), cough severity using the Visual Analog Scale (MD = -13.36, 95% CI [-17.80, -8.92], P < 0.00001), cough severity diary (MD = -0.88, 95% CI [-1.25, -0.51], P < 0.00001), and total LCQ score (MD = 2.00, 95% CI [1.15, 2.86], P = 0. 00001). Meta-regression analyses showed a positive correlation between the gefapixant dose and the incidence of any adverse event (relative risk [RR] = 0.239, 95% CI [0.093, 1.839], P = 0.001) and incidence of adverse event related to treatment (RR = 0.520, 95% CI [0.117, 0.922], P = 0.011). CONCLUSIONS: In patient with chronic cough, gefapixant exhibits favorable anti-tussive outcomes by improving the cough frequency, severity, and quality of life. While gefapixant is largely tolerable, its side effects (notably taste alteration) are dose dependent.